外用联合靶向 siRNA治疗生殖器疱疹豚鼠模型实验.pdfVIP

外用联合靶向siRNA治疗生殖器疱疹豚鼠模型实验

李淑林;韩建德;廖绮曼;李欢;李茵茵;李红梅;马春光;陈木开

【摘要】目的:评价联合靶向特异性小干扰RNA(HSV-2UL27.2和UL29.2基因)

对生殖器疱疹(GH)模型的疗效.方法:(1)病毒攻击实验:雌性豚鼠60只,随机分为

治疗组和对照组,每组30只,治疗组小鼠外阴和阴道内外用联合靶向特异性小干扰

RNA(CT-siRNA),对照组外用非靶向基因的RNA制剂(siN.C),作用4小时后接种疱

疹病毒2型(HSV-2)野生株,观察豚鼠发病情况并计算生存率.(2)选取接种HSV-2

后具有初发GH反应的雌性豚鼠60只,分为治疗组和对照组,每组30只,分别外用

CT-siRNA和siN.C制剂,每周1次至皮损愈合.2个月后小鼠腹腔内注射环磷酰胺

并给予紫外线照射诱导复发,计算疱疹复发率.结果:病毒攻击感染后治疗组存活率

(80.0%)高于对照组(23.3%)(P0.05).治疗第10天治疗组皮损积分值

(0.25±0.25)较对照组明显降低(1.0±1.25)(P0.05).诱导复发后,治疗组复发率

(16.7%)低于对照组(60.0%)(P0.05).结论:外用CT-siRNA制剂能预防HSV-2的

感染及复发.%Objective:ToassesstheeffectofcombinedtargetingsiRNA

(CT-siRNA,HSV-2UL27.2genecombinedUL29.2gene)ongenitalherpes

ofguineapig.Methods:(1)HSV-2infectionexperiment:sixtyguineapigs

weredividedintothetreatmentgroupandcontrolgroup(30ineach

group).GuineapigsinthetreatmentgroupweretreatedwithtopicalCT-

siRNAonvulvaandvaginaandthoseinthecontrolgroupweretreated

withsiN.C.After4hours,theherpesvirustype2(HSV-2)wildstrainswere

inoculatedtovagi-nainalltheguineapigs.(2)Sixtyguineapigmodels

withtheinfectionofgenitalherpesweredividedintothetreatmentgroup

andcontrolgroup(30guineapigsineachgroup).Guineapigsinthe

treatmentgroupweretreatedwithtopicalCT-siRNAonvaginaandthose

inthecontrolgroupweretreatedwithsiN.C,onceaweekuntillesion

healing.Allguineapigsweretreatedwithintraperitonealinjectionsof

cyclophosphamideandultra-violetradiationtoinducetherecurrenceafter

the2monthtreatmentandtherecurrenceratewasassessed.Re-sults:The

survivalrateinthetreatmentgroupwas80%,whichwashigherthanthat

inthecontrolgroup(23.3%),(P0.05).Atday10ofthetreatment,the

lesionsscoreinthetreatmentgroupwas(0.25±0.25),whichwaslower

thanthatinthecontrolgroup(1.0±1.25)(P0.05).